The present invention relates generally to the fields of biomedical physics and drug delivery. More specifically, the present invention relates to laser probes for drug permeation for local administration.
It is an axiom in pharmaceutical science that it is usually beneficial to maximize the local concentration of a biologically active material (pharmaceutic or biologic) in the tissue volume of interest. Similarly, it is typical that local administration is more desirable than systemic administration since the latter requires a higher dosage necessary for a therapeutic treatment, and often leads to an increase in side effects either systemically or at specific sites distal from the target tissue. However, local delivery of compounds is often not practical because the compounds do not significantly penetrate target tissues or tissues adjacent to or surrounding the site of interest.
Recently, multiple methods of making tissue more permeable to topically applied compounds were discovered. These methods can involve irradiating the tissue with the radiant energy produced by a laser before, during, or after drug administration. While these methods have been described elsewhere, the devices to make the methods feasible have not.
Chemotherapeutic drugs which exhibit a significant therapeutic effect are commonly used in cancer treatment. However, side effects and systemic dosage toxicity remain a problem in chronic treatment of disease. It is therefore beneficial to administer such drugs locally and in high concentrations for the more direct treatment of solid tumors. Local therapies are generally ineffective due to the difficulty to deliver the drugs to a local environment. Furthermore, tumor tissues are typically less vascularized, which results in poor drug uptake. Therefore, a means to enhance the tumor uptake of locally administered drugs, or even of drugs administered systemically, could result in increased efficacy and decreased systemic toxicity due to the lower dosage that is required.
Bone and joint infections include two disease processes known respectively as osteomyelitis and septic or infectious arthritis. As such, they are unique and separate infectious entities with different signs and symptoms caused by different infectious agents. Together these diseases affect more than 100,000 Americans annually. Introduction of oral antibiotic therapy has had a dramatic impact on these diseases. However, these diseases continue to cause a significant morbidity due to residual damage and chronic recurring infections.
The bone may be predisposed to infection through trauma such as a puncture wound or during surgery. However, infection may also reach the bone from adjoining soft tissue or from the bloodstream resulting in osteomyelitis. Infectious arthritis, on the other hand, is usually acquired from hematogenous spread. Chronic infection can persist for years. Patients with chronic osteomyelitis have a very poor prognosis. Dead bone and other necrotic material from the infection act as a bacterial reservoir and make the infection difficult to eliminate.
The patients are treated to eliminate the infection and prevent the development of chronic infection through high-dose intravenous antibiotics and/or surgical removal of dead bone tissue. Bone is a highly vascular mineralized connective tissue with internal trabeculae (where bone marrow and blood supply is situated) and a surrounding layer of solid cortical bone. Nevertheless, bone is less vascularized in advanced stages of disease, which makes it difficult to achieve high antibiotic concentrations. Therefore, methods and devices that improve the penetration of antibiotics in advanced stages of disease and deliver a high local concentration of antibiotic would be highly desirable.
Earaches in children are usually a result of otitis media, which commonly occurs when the eustachian (i.e. pharyngotympanic) tube (i.e., the narrow tube that connects the middle ear to the nasopharynx) becomes blocked. The blockage prevents fluid from draining out of the tube, which leads to bacterial or viral infection. More than 75% of children have at least one ear infection by their third birthday and almost 50% of children have had three or more infections before the age of three. Further, as the infection progresses, the bone may become involved resulting in significant permanent damage. A common complication of otitis in children is hearing loss. Recent studies indicate that up to 40% of children in the U.S. may have had some hearing loss due to infection. This hearing loss may be severe where infections are recurring or left untreated.
The treatment for earaches involves analgesics and oral antibiotics, a practice that is increasingly under scrutiny because of the related risks of developing resistance to antibiotics. In some cases, pressure-equalization (PE) tubes are inserted to drain fluids, pressure-equalization tubes, which are left in place for 6-9 months, perforate the tympanic membrane to allow fluid to drain. The placement of pressure-equalization tubes is done under general anesthesia, which has associated risks. The procedure itself may also lead to hearing defects. Topical administration of antibiotic to the tympanic membrane is impractical as the membrane is quite impermeable, and treatment of deep infection is limited due to large quantities required to be given orally. Thus, a means for delivering high local concentrations of drugs to the tympanic membrane would be useful for treating deep infections and preventing tissue damage.
Oral administration, the common route in drug administration, can sometimes be impractical. Other routes of administration might be more attractive under some pharmacokinetic issues. For example, rectal administration of drugs is potentially useful due to the rate and extent of rectal drug absorption. However, drug administration by this route can be problematic since the rectal mucosa is inherently not permeable. The most important clinical situation where rectal administration is desirable is in the case of pediatric or neonatal patients who cannot, or refuse to take oral medications. An effective means for delivering therapeutically active substances across the rectal mucosa would therefore be highly desirable for delivering a range of drugs to infants.
The prior art is deficient in the lack of effective means of enhancing local administration of pharmaceuticals and/or collection of biological materials. The present invention fulfills this long-standing need and desire in the art.
The present invention provides methods and devices for enhancing the local administration of pharmaceuticals or collection of biological materials from the body for therapeutic or diagnostic purposes. Pharmaceuticals or biological materials diffuse through membranes or anatomical structures which are not normally amenable to local drug administration or biomaterial collection.
The present invention further provides applications of the methods/devices in treating diseases such as solid cancers, bone infection and ear infection.
In one embodiment of the present invention, there is provided an optical device for enhancing delivery of a compound to or from a subject locally, comprising an optical probe with a tip; a source for radiant energy; a catheter for delivering the compound to or from the tip; a catheter for delivering radiant energy to the tip; and a means to observe placement of the tip. Optionally, the tip is further encased in a biocompatible sleeve. Alternatively, the tip is in contact with or be surrounded by a radiant energy absorbing material.
In another embodiment of the present invention, there is provided a method for enhancing delivery of a pharmaceutical compound to a subject locally, comprising the steps of irradiating the subject with radiant energy and administering a pharmaceutical compound to the subject, wherein both the radiant energy and pharmaceutical compound are delivered through the optical device disclosed above. Such method may be used for treating a solid tumor, a bone disease and an ear disease, or enhancing rectal administration of a pharmaceutical compound in an individual. For doing so, the optical device disclosed above is modified to fit each individual situation.
In still another embodiment of the present invention, there is provided a method for increasing diffusion rate of a substance in a medium, comprising the step of applying radiant energy to the medium, wherein the radiant energy generates propagating pressure wave upon the medium and is delivered through the optical device disclosed herein.
In yet another embodiment of the present invention, there is provided a method for improving permeation rate of a molecule through a barrier, comprising the step of applying radiant energy to the barrier, wherein the radiant energy is delivered through the optical device disclosed herein and ablates or alters the structure of the barrier.
In still yet another embodiment of the present invention, there is provided a method for creating pores in a barrier thereby improving permeation rate of a molecule through the barrier, comprising the step of applying radiant energy to the barrier, wherein the radiant energy is delivered through the optical device disclosed herein.
Other and further aspects, features, and advantages of the present invention will be apparent from the following description of the presently preferred embodiments of the invention given for the purpose of disclosure.